The project is designed to investigate factors operating at the plasma membrane which regulate iron uptake by erythroid cells at different stages of erythroid development. In particular, I intend 1) to further establish that glycophorin, the major glycoprotein of red blood cell membranes, is the transferrin receptor; 2) to determine the factors that regulate the binding of the plasma iron carrier transferrin to its receptor on erythroid cells at different stages of erythroid differentiation, and 3) to purify and characterize and erythroid plasma membrane protein which acts as intermediate in the passage of iron through the plasma membrane. As a result of these investigations, a greater understanding of the normal mechanisms of iron uptake will be achieved. This knowledge could then be applied to study variations of normal iron metabolism such as iron deficiency and the sideroblastic anemias as well as variations of normal iron metabolism in transformed erythroid cell lines such as Friend and Rauscher murine erythroleukemias and the K562 human erythroleukemia.